the role of cell-cycle delay in altering response or affecting risk associated with indoor exposure to radon is not clear. However, most respiratory tract epithelial cells have rather long cell-turnover times of about 30 days (Adamson 1985), and spend only a small fraction of the total time in stages of the cell cycle that are most radiation sensitive. Inasmuch as the dose rate and number of traversals per cell are very low in the respiratory tract, the probability of alpha-particle traversal in a cycling cell is very low. In addition, the efficiency of cell killing by alpha particles might also decrease the relevance of cell-cycle delay to a risk assessment model. Those considerations make it likely, although not certain, that cell-cycle delay produced by environmental radon exposure plays a minor role in changing potential response or risk.
After exposure to ionizing radiation, mammalian cells die by one of 2 distinct processes. The classic form of death has been called ''mitotic death"; cells die in attempting to divide as a consequence largely of complex chromosomal aberrations (Carrano and Heddel 1973). An alternative mode of death is by "apoptosis," or programmed cell death (Stewart 1994), which involves a characteristic progression of phenotypic changes, including induction of DNA fragmentation and the cell finally being phagocytosed by its neighbors. The relative importance of the 2 modes of cell death varies widely. For some cell types, apoptosis dominates; for others, apoptosis is seldom seen; in yet others, they are about equal. In most self-renewal tissues, apoptosis is a common mechanism to remove damaged or unwanted cells. Radiation-damaged cells are no exception. Failure of processes that lead to apoptotic death and removal of the damaged cells presents an alternative pathway to carcinogenesis for a radiation-damaged cell (Thompson 1995). While apoptosis is generally associated with doses significantly higher than doses usually attributed to radon progeny, apoptosis might be present at low doses.
It has been demonstrated that changes in regulation of cell proliferation play an important role in the development of cancer (Brooks and others 1982; Cohen and others 1992), and it has been suggested that changes in cellular proliferation can be used in risk assessment of exposures to carcinogens (Clayson and others 1989; Clifton and others 1991; Goldsworthy and others 1991). It has also been established that an increase in cell turnover in the upper and lower respiratory tract follows experimental inhalation of radon (Taya and others 1994) and that, in the nose and upper respiratory tract, this increase is related to the areas with the highest radiation dose (Atencio 1994).